tbuckley/cabot-search huggingface dataset:
Towards zero carbon healthcare: anaesthesia
Authors: Clifford L Shelton, Rebecca Knagg, Rakesh V Sondekoppam, Forbes McGain
Journal: BMJ (2022)

What you need to know• Sevoflurane and isoflurane have smaller atmospheric impacts than desflurane and nitrous oxide • Intravenous anaesthetic agents have minimal atmospheric impacts, but drug waste and urinary excretion of drugs and metabolites causes pollution in soil and ground water • Nitrous oxide is a common cause of medication waste and greenhouse gas emissions due to leaks in supply systems, over-ordering, and unused gas in cylinders returned to suppliers being vented to the atmosphere Case 1-A 30 year old woman attends the obstetric anaesthetic clinic at 36 weeks' gestation.This is her first pregnancy.The baby was in the breech position, and, after an unsuccessful attempt to turn the baby, she has been offered the option of planning for a vaginal delivery or a caesarean section.The anaesthetist discusses the anaesthetic and analgesic options for both and reassures the patient that all options appropriate to the mode of delivery are safe.Her priority is a safe delivery but she recently read online that both anaesthetic agents and "gas and air" contribute to global warming.Concern about the world in which her child will grow prompts her to ask which is the "greenest" option.Case 2-A 55 year old man is listed for total knee replacement for osteoarthritis, which is limiting his mobility and affecting his ability to pursue his passion for fell walking.When offered a choice of spinal or general anaesthesia, he says he has no preference providing both are safe, but he has noticed the enormity of hospital waste and asks which is the most sustainable option.Providing anaesthesia for approximately 310 million surgical procedures worldwide every year, 1 and contributing to peri-operative medicine, critical care, and pain management, generates emissions of greenhouse gases (GHGs) and vast amounts of waste.In this paper, we suggest ways that anaesthesia teams can mitigate their environmental footprints while integrating their primary aim of providing safe, high quality patient care. What is the evidence?Life cycle assessments of the "carbon footprints" of anaesthetic equipment, medications, and procedures, 2 3 global endorsement of sustainable anaesthesia practice, 4 and expanding literature on the atmospheric effects of inhalational anaesthetics 5 -8 show the problem; however, strong evidence for specific solutions is relatively sparse and novel compared with other aspects of healthcare. 4 9 10MAC=minimum alveolar concentration; the mean percentage end-tidal anaesthetic agent concentration at which a patient of 40 will be unresponsive to surgical stimulation
Medical micro- and nanomotors in the body
Authors: Huaan Li, Fei Peng, Xiaohui Yan, Chun Mao, Xing Ma, Daniela A. Wilson, Qiang He, Yingfeng Tu
Journal: Acta Pharmaceutica Sinica B (2022)

Attributed to the miniaturized body size and active mobility, micro- and nanomotors (MNMs) have demonstrated tremendous potential for medical applications. However, from bench to bedside, massive efforts are needed to address critical issues, such as cost-effective fabrication, on-demand integration of multiple functions, biocompatibility, biodegradability, controlled propulsion and in vivo navigation. Herein, we summarize the advances of biomedical MNMs reported in the past two decades, with particular emphasis on the design, fabrication, propulsion, navigation, and the abilities of biological barriers penetration, biosensing, diagnosis, minimally invasive surgery and targeted cargo delivery. Future perspectives and challenges are discussed as well. This review can lay the foundation for the future direction of medical MNMs, pushing one step forward on the road to achieving practical theranostics using MNMs.
Climate policy and activism need to make space for disabled people
Authors: Pauline Castres
Journal: BMJ (2022)

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The <i>Drosophila</i> DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3′ untranslated region (3′UTR) of <i>Dscam</i> mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic analysis shows that Wnd requires <i>pAbp</i> for promoting presynaptic arbor growth and for enhancing Dscam expression. Our analysis revealed that <i>Dscam</i> mRNAs harbor short poly(A) tails. We identified a region in <i>Dscam</i> 3′UTR that specifically interacts with pAbp. Removing this region significantly reduced Wnd-induced increase in Dscam expression. These suggest that a noncanonical interaction of PABP with the 3′UTR of target transcripts is essential for DLK functions. <b>SIGNIFICANCE STATEMENT</b> The kinase DLK plays key roles in a multitude of neuronal responses, including axon development, neurodegeneration, and nerve injury. Previous studies show that DLK acts via mRNAs to regulate protein synthesis, but how DLK does so is poorly understood. This study demonstrates that DLK regulates the synthesis of Dscam through the poly(A)-binding protein PABP-C. Whereas PABP-C is known as a general translational activator, our study shows that DLK-mediated Dscam expression involves a noncanonical interaction between PABP-C and the <i>Dscam</i> mRNA, which leads to a selective regulation of <i>Dscam</i> translation by PABP-C. Thus, our study provides novel insights into the mechanisms that underlie the function of DLK and regulation of gene expression of PABP-C.
G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes
Authors: Xiaoli Wei, Fan Yin, Miaomiao Wu, Qianqian Xie, Xueqin Zhao, Cheng Zhu, Ruiqian Xie, Chongqing Chen, Menghua Liu, Xueying Wang, Ruixue Ren, Guijie Kang, Chenwen Zhu, Jingjing Cong, Hua Wang, Xuefu Wang
Journal: Acta Pharmaceutica Sinica B (2022)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35–STARD4 axis is a promising therapeutic target for NAFLD.
CTpathway: a CrossTalk-based pathway enrichment analysis method for cancer research
Authors: Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-e Huang, Fei Hou, Christine M. Eischen, Wei Jiang
Journal: Genome Medicine (2022)

Abstract Background Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated. Methods To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with &gt;440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in GPCM, we assign a risk score to genes in the GPCM and identify risk pathways enriched with the risk genes. Results Analysis of &gt;8300 expression profiles covering ten cancer tissues and blood samples indicates that CTpathway outperforms the current state-of-the-art methods in identifying risk pathways with higher accuracy, reproducibility, and speed. CTpathway recapitulates known risk pathways and exclusively identifies several previously unreported critical pathways for individual cancer types. CTpathway also outperforms other methods in identifying risk pathways across all cancer stages, including early-stage cancer with a small number of differentially expressed genes. Moreover, the robust design of CTpathway enables researchers to analyze both bulk and single-cell RNA-seq profiles to predict both cancer tissue and cell type-specific risk pathways with higher accuracy. Conclusions Collectively, CTpathway is a fast, accurate, and stable pathway enrichment analysis method for cancer research that can be used to identify cancer risk pathways. The CTpathway interactive web server can be accessed here http://www.jianglab.cn/CTpathway/ . The stand-alone program can be accessed here https://github.com/Bioccjw/CTpathway .
Workforce: RCP demands immediate action and plan to keep NHS running
Authors: Gareth Iacobucci
Journal: BMJ (2022)

The government must commit to publishing a long term NHS workforce plan by the end of this year or face long waiting times becoming normal, the Royal College of Physicians of London has warned. In a new policy paper the RCP said that a long term plan for increasing staff numbers and expanding medical school places was vital.1 Given the urgency of the situation, the RCP also set out a range of short to medium term solutions (box 1) that the government must implement now to keep the NHS running, ranging from affordable childcare and flexible working to overseas recruitment and a new “retire and return” deal for consultants. Box 1 ### RCP’s short and medium term solutions for boosting NHS workforce #### Actions to increase staff numbersRETURN TO TEXT
A homozygous truncating mutation of FGL2 is associated with immune dysregulation
Authors: Erin Janssen, Mohammad F Alosaimi, Anas M Alazami, Abdullah Alsuliman, Ayodele Alaiya, Bandar Al-Saud, Hamoud Al-Mousa, Tariq Jassim Al-Zaid, Emma Smith, Craig D Platt, Hibah Alruwaili, Sarah Albanyan, Sulaiman M Al-Mayouf, Raif S Geha
Journal: Journal of Allergy and Clinical Immunology (2022)
Author Correction: Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG
Authors: Zhana Duren, Fengge Chang, Fnu Naqing, Jingxue Xin, Qiao Liu, Wing Hung Wong
Journal: Genome biology (2022)

Following publication of the original paper [1], the authors have reported an error in reference genome version of the HiC data used for validation of the RE-TG interactions.After using the correct version of the HiC anchor locations, the result in Fig. 4D, supplementary Figure S11, and S12 are all improved.
Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study
Authors: Renaud Tamisier, Jean-Louis Pépin, Holger Woehrle, Muriel Salvat, Gilles Barone-Rochette, Cécile Rocca, Eik Vettorazzi, Helmut Teschler, Martin Cowie, Patrick Lévy
Journal: European Respiratory Journal (2022)

Background Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA. Methods HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea–hypopnoea index (AHI) ≥15 events·h −1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed. Results 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h −1 ). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min −1 at baseline to 44.6±11.2 bursts·min −1 ; ASV group: 43.0±9.0 bursts·min −1 at baseline to 42.74±9.45 bursts·min −1 ). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective. Conclusions Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality.
Calcium Hydride‐Based Dressing to Promote Wound Healing
Authors: Fei Gong, Nailin Yang, Jiachen Xu, Xiaoyuan Yang, Kailu Wei, Linqian Hou, Bo Liu, He Zhao, Zhuang Liu, Liang Cheng
Journal: Advanced Healthcare Materials (2022)

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H2 ) with effective ROS scavenging and calcium hydride (CaH2 ) with sufficient H2 supply, the authors for the first time employed CaH2 as a therapeutic H2 donor and starch as a diluent to construct CaH2 pulvis dressing for wound healing treatment. It has been found that CaH2 by generating H2 exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death. After being applied onto the skin wound, the CaH2 pulvis dressing with the unique ROS-scavenging ability can accelerate skin wound healing in healthy/diabetic mice (small animal models) and Bama mini-pigs (large animal model). Such CaH2 dressing can release H2 to relieve the inflammation levels, decrease the secretion of pro-inflammatory cytokines, increase the infiltration of inflammation-suppressive immune cells, and promote the regeneration of new blood vessels and collagens, thereby accelerating wound healing. This work highlighted that the integration of anti-oxidation and anti-inflammation functions based on CaH2 dressing endowed it with a promising possibility for the treatment of inflammatory diseases.
In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
Authors: Rishi Chanderraj, Jennifer M. Baker, Stephen G. Kay, Christopher A. Brown, Kevin J. Hinkle, Daniel J. Fergle, Roderick A. McDonald, Nicole R. Falkowski, Joseph D. Metcalf, Keith S. Kaye, Robert J. Woods, Hallie C. Prescott, Michael W. Sjoding, Robert P. Dickson
Journal: European Respiratory Journal (2022)

Background Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. Methods We conducted a retrospective single-centre cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. We compared intensive care unit outcomes (ventilator-associated pneumonia (VAP)-free survival, infection-free survival and overall survival) in all patients and changes in gut microbiota in a subcohort of 116 patients. In murine models, we studied the effects of anaerobe depletion in infectious ( Klebsiella pneumoniae and Staphylococcus aureus pneumonia) and noninfectious (hyperoxia) injury models. Results Early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival (hazard ratio (HR) 1.24, 95% CI 1.06–1.45), infection-free survival (HR 1.22, 95% CI 1.09–1.38) and overall survival (HR 1.14, 95% CI 1.02–1.28). Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011) and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic-treated patients (p&lt;2.2×10 −16 ). In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p&lt;0.05) and increased the lethality of hyperoxia (p=0.0002). Conclusions In critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered.
A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)
Authors: Jatin Patel, Damon Bass, Albertus Beishuizen, Xavier Bocca Ruiz, Hatem Boughanmi, Anthony Cahn, Hugo Colombo, Gerard J. Criner, Katherine Davy, Javier de-Miguel-Díez, Pablo A. Doreski, Sofia Fernandes, Bruno François, Anubha Gupta, Kate Hanrott, Timothy Hatlen, Dave Inman, John D. Isaacs, Emily Jarvis, Natalia Kostina, Tatiana Kropotina, Jean-Claude Lacherade, Divya Lakshminarayanan, Pedro Martinez-Ayala, Charlene McEvoy, Ferhat Meziani, Mehran Monchi, Sumanta Mukherjee, Rosana Muñoz-Bermúdez, Jessica Neisen, Ciara O'Shea, Gaëtan Plantefeve, Lorrie Schifano, Lee E. Schwab, Zainab Shahid, Michinori Shirano, Julia E. Smith, Eduardo Sprinz, Charlotte Summers, Nicolas Terzi, Mark A. Tidswell, Yuliya Trefilova, Russell Williamson, Duncan Wyncoll, Mark Layton
Journal: European Respiratory Journal (2022)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19.
Pulse oximeter measurement error of oxygen saturation in patients with SARS-CoV-2 infection stratified by smoking status
Authors: Colin J. Crooks, Joe West, Joanne R. Morling, Mark Simmonds, Irene Juurlink, Steve Briggs, Simon Cruickshank, Susan Hammond-Pears, Dominick Shaw, Timothy R. Card, Andrew W. Fogarty
Journal: European Respiratory Journal (2022)

As pulse oximeters are now so widely used, it is important to identify any patient groups in whom they may also have a systematic bias that may impair the delivery of medical care to these individuals. One group would be tobacco smokers [1–3], as the inhaled carbon monoxide modifies the haemoglobin molecule within 1–2 min of inhaling tobacco smoke [4], and the subsequent increase in blood carboxyhaemoglobin levels modifies the pulse oximetry signal [5]. This was reported in a series of 16 patients with carbon monoxide poisoning from 1994 which resulted in higher pulse oximetry measurements than the true values, with the comment that this phenomenon may also extend to oxygen saturation measured in smokers as well [6]. To date, no robust real-world clinical data on acutely unwell patients exist to clarify the impact of smoking status and blood carboxyhaemoglobin levels on the measurement error of oxygen saturation by pulse oximeters. There is substantial measurement error in pulse oximetry readings of oxygen saturation below 90% which is not due to smoking status https://bit.ly/3RunKtL The authors would like to thank an anonymous reviewer whose insightful comments changed the whole outcome of this analysis.
ERS/ESTS statement on the management of pleural infection in adults
Authors: Eihab O. Bedawi, Sara Ricciardi, Maged Hassan, Michael R. Gooseman, Rachelle Asciak, Olalla Castro-Añón, Karin Armbruster, Martina Bonifazi, Sarah Poole, Elinor K. Harris, Stefano Elia, Rafal Krenke, Alessandro Mariani, Nick A. Maskell, Eva Polverino, Jose M. Porcel, Lonny Yarmus, Elizabeth P. Belcher, Isabelle Opitz, Najib M. Rahman
Journal: European Respiratory Journal (2022)

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.
Effectiveness of treatments for people living with severe dementia: A systematic review and meta-analysis of randomised controlled clinical trials
Authors: Elena Profyri, Phuong Leung, Jonathan Huntley, Vasiliki Orgeta
Journal: Ageing Research Reviews (2022)

Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited.